The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis

Garcês, Sandra; Demengeot, Jocelyne; Benito-Garcia, Elizabeth

doi:10.1136/annrheumdis-2012-202220

Cited by 354 publications

(269 citation statements)

References 60 publications

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“…In a metaanalysis that evaluated the presence and effects of anti-drug antibodies in patients with different inflammatory diseases, such as rheumatoid arthritis, spondyloarthropathies and inflammatory bowel diseases, the drug response was reduced if anti-drug antibodies could be detected in the sera of patients. Among different diseases the effect of anti-drug antibody positivity on TNFi responses was more pronounced in AS and spondyloarthropathies than in other diseases (27). As concomittant treatment with methotrexate or other immunosuppressive drugs reduces the production of these antibodies, and as in axial form of spondyloarthropathies these type of drugs are usually not administered, it may highlight the necessity of determination of anti-drug antibodies in cases of loss of efficacy in AS, which may give further support for the decision of switching.…”

Section: Discussionmentioning

confidence: 93%

Real-life experience with switching TNF-α inhibitors in ankylosing spondylitis

et al. 2014

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Objective: The aim of this study was to evaluate efficacy, reasons for switching and drug survival of TNF-α inhibitors (TNFi-s) used as first and second line drugs in ankylosing spondylitis (AS).Methods: Data of patients suffering from AS and treated with at least one TNFi between November 2005 and November 2013 were extracted retrospectively from the database of one clinical center. Beside demographic data, the disease activity measured by BASDAI, the response rates (BASDAI50), reasons for switching and survival curves of TNFi-s were analyzed in general and in subgroups of patients treated with each of the available TNFi-s. The reasons for switching were defined as inefficacy, side effect of the given drug, patient's request, and occurence of extra-articular manifestations.Results: Altogether 175 patients were on TNFi and 77 of them received at least 2 TNFi-s. The patients' age at the initiation of the first TNFi was higher among switchers compared to nonswitchers (42.5±12.6 vs 38.8±11.2 years, p=0.049), otherwise gender, disease duration and initial disease activity had no influence on the risk of switching. The decrease of BASDAI was similar among non-switchers and switchers either using the first or second TNFi, but the response rates to the first and second TNFi were worse in switchers than in non-switchers. Following the failure of first TNFi, the retention on therapy was unfavourable, especially in patients on infliximab after one year of treatment. The main reason for switching from the first drug was inefficacy. The frequency of side effects that led to switching was higher in the infliximab group than in patiets treated with other agents. Conclusion:Although the retention rate to a second line TNFi was somewhat worse than that to the first line TNFi, switching of TNFi-s is a good therapeutic option is AS patients who failed to respond to the first TNFi.

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Section: Discussionmentioning

confidence: 93%

Real-life experience with switching TNF-α inhibitors in ankylosing spondylitis

et al. 2014

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“…Numerous literature reports have stated that immunogenicity negatively impacted the therapeutic outcomes of biological treatments, such as immunogenicity-associated secondary treatment failure (5,7,8) for monoclonal antibodies and recombinant proteins. A reduction in the systemic exposure can be associated with the observed immunogenicity and a potential explanation for the reduced efficacy to biologics.…”

Section: Introductionmentioning

confidence: 99%

Evaluating and Reporting the Immunogenicity Impacts for Biological Products—a Clinical Pharmacology Perspective

Wang

Hon

et al. 2015

AAPS J

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Abstract. Immunogenicity assessment is important for biological products due to potential impacts of immunogenicity on safety and efficacy. We reviewed the prescribing information and the FDA's clinical pharmacology review of 121 approved biological products for evaluating and reporting of immunogenicity data. Of the 121 products, 89% (n = 108) reported the incidence of immunogenicity and 49% (n = 59) reported immunogenicity impact on efficacy. However, only 26% (n = 31) reported whether the immunogenicity affected pharmacokinetics. A subset of 16 products reported effects of anti-drug antibodies (ADA) on both systemic clearance and efficacy; 8 of 16 products had increased systemic clearance coinciding with reduced efficacy, and 6 of 16 products had no changes in either clearance or efficacy. Factors contributing to infrequent reporting of the ADA effect on exposure and methods for determining the effect of ADA on exposure are summarized. Measuring ADA and drug concentrations concurrently over time enables the evaluation of ADA impact on pharmacokinetics. Within-subject comparison of concentration data (before vs. after ADA formation) is a useful alternative to betweensubject (ADA+ vs. ADA−) comparison when sample size is limited or when the majority of subjects developed ADA. The biological complexity of immune responses presents challenges to quantifying the ADA impact on pharmacokinetics using model-based methods. Our findings support that pharmacokinetic exposure is more sensitive than efficacy endpoints for evaluating ADA effects. A decrease in drug concentration due to formation of ADA during treatment can serve as an early indicator for potential reduced efficacy occurring at a later time.KEY WORDS: clinical pharmacology assessment; immunogenicity data for approved biological products; impact on clinical pharmacokinetics and efficacy; incidence of anti-drug antibodies and neutralizing antibodies.

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“…12 In Garces et al research, ETN effects were found less atherogenic than infliximab which supports our findings in this case. 13 They showed a prominent increase in HDL after 1 year of ETN treatment and showed no change in cholesterol and LDL levels. Our case also showed an improvement in HDL-C levels under ETN treatment.…”

Section: Discussionmentioning

confidence: 92%

A psoriatic arthritis patient who developed hypertriglyceridemia while receiving adalimumab treatment

Mercantepe¹,

Topaloğlu²,

Yıldırım³

et al. 2017

Int J Res Med Sci

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Anti-TNF agents have prominent effect on inflammatory diseases and they probably have various effects on lipid metabolism. Adalimumab (ADA) is the first fully human TNF-alfa antagonist. Our study presents a male patient who developed evident hypertriglyceridemia while receiving ADA treatment. We retrospectively collected data of one psoriatic arthritis patient treated with adalimumab at the University Hospital of Recep Tayyip Erdogan (November 2016). Adalimumab treatment significantly increased triglyceride from 278mg/dl to 4046mg/dl. The influence of adalimumab treatment on lipid profile seems to be proatherogenic, but further investigation is needed to confirm this hypothesis.

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The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis

Abstract: ADA reduces drug response, an effect that can be attenuated by concomitant immunosuppression, which reduces ADA frequency. Drug immunogenicity should be considered for the management of patients receiving biological therapies.

Cited by 354 publications

References 60 publications

Real-life experience with switching TNF-α inhibitors in ankylosing spondylitis

Real-life experience with switching TNF-α inhibitors in ankylosing spondylitis

Evaluating and Reporting the Immunogenicity Impacts for Biological Products—a Clinical Pharmacology Perspective

A psoriatic arthritis patient who developed hypertriglyceridemia while receiving adalimumab treatment

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